Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of species II in the reply filed on November 4, 20225 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 7 and 15 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 4, 2025.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 102 which forms the bases of rejections set forth in this Office action.
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 3 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis”, Audrea Augello et. al., 2007, hereinafter Augello
Regarding claim 1, Augello et al. teaches a method of stem cell therapy for treatment of cartilage degenerative disease in a patient (page 1175, column 1, paragraph 1) comprising:
a) assessing and quantifying levels of pro-inflammatory and anti-inflammatory mediators in systemic circulation and/or local micro-environment (page 1177, column 2, paragraph 6, which teaches testing and determining concentration of IL-2 Il-4, IL-10 and IFNγ); and
b) administering bone marrow cells as stem cell therapy to said patient (page 1183, column 2, paragraph 5, which teaches administering mesenchymal stem cells (MSC) for the treatment of collagen-induced arthritis (CIA). Therefore, the limitations of part a and b are met.
Regarding claim 3, Augello teaches wherein said stem cell therapy is allogenic administration of bone marrow derived mesenchymal stem cells (paragraph 3, column 2 p.1176, which teaches collecting bone marrow derived mesenchymal stem cells (MSCs) and culturing them for use of allogenic administration) and (paragraph 4, column 2, p. 1176 only selecting MSCs with potential for differentiation for experimentations). Therefore, the limitations of claim 3 are met.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis”, Audrea Augello et. al., 2007, hereinafter Augello in view Cellular and Clinical Analyses of Autologous Bone Marrow Aspirate Injectate for Knee Osteoarthritis: A Pilot Study”, Kristina Wells et. al., 2020, hereinafter Wells
Regarding claim 2, Augello teaches using stem cell therapy administration using from mesenchyme stem cells (paragraph 3, column 1 p. 1175 teaches an approach to target the pathogenic mechanisms of autoimmune arthritis using allogenic MSCs.) Augello (paragraph 3, column 1, p.1175 uses a stem cell therapy administration where the bone marrow stem cells are not endogenous and later used for therapy in a subject.) Augello does not teach autologous administration of bone marrow aspirate/mononuclear cells.
Wells (abstract) teaches the characterization of the cellular content of bone marrow aspirate (BMA) and to evaluate the effect of intra-articular autologous BMA injections in patients with mild knee osteoarthritis (OA). Wells (paragraph 6, p. 7) teaches clinical significance (see Table 4) and improvements in current numerical rating scale (NRS) pain was achieved in 3-, 6-, and 12-months post-procedure. Moreover, Wells (paragraph 2, p. 2) teaches bone marrow aspirate (BMA) intra-articular injection appear to be safe with potential therapeutic value.
Therefore, it would be obvious before the effective filling date of the claim invention for ordinary person skill in the art to implement the use of autologous administration of bone marrow aspirate/mononuclear cells for stem cell therapy because Wells (see table 4, teaches improvements in current numerical rating scale (NRS) pain was achieved in 3-, 6-, and 12-months post-procedure). Moreover, Wells (paragraph 2, p. 2) teaches bone marrow aspirate (BMA) intra-articular injection appear to be safe with potential therapeutic value.
Claim(s) 4 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis”, Audrea Augello et. al., 2007, hereinafter Augello, in view of Correlation of Plasma Interleukin1 levels with Disease Activity in Rheumatoid Arthritis”, Julie A. Eastgate et. al., 1988 hereinafter Eastgate
Regarding claim 4 Augello (paragraph 2, column 1 p. 1176 discloses susceptibility of Collagen induced arthritis (CIA) in rodents and humans is linked to MHC and the immune response to type II collagen (CII) is due to both stimulation of collogen-specific T cells and the production do high titers of specific antibodies). Additionally, Augello (paragraph 7, column 2 p.1177 teaches concentrations of IL-2, IL-4, IL-10, and interferon-γ, and IFNα in supernatants of CII-primed T lymphocytes in vitro rechallenged with CII were assessed). Augello does not teach quantitation and assessing of proinflammatory mediators in plasma levels of IL-1β.
Eastgate (paragraph 4, column 1, p.707) teaches the extraction procedure increased the detection of plasma IL-1 beta both in RA patients and in controls and that plasma IL-1 levels were higher in patients, and sought correlations between plasma IL-1 beta concentration and conventional indices of disease activity in the RA patients). Moreover, Eastgate (paragraph 5, column 1, p.707) teaches plasma IL-1 beta correlations with disease activity (see Fig. 1).
Therefore, it would have been obvious before the effective filling date of the claimed invention to use plasma levels to assess proinflammatory cytokine IL-1β because (Eastgate paragraph 4 column 1, p.708) teaches the extraction procedure increased the detection of plasma IL-1 beta which (Eastgate, abstract) correlates with disease activity.
Regarding claim 5 Augello (paragraph 6, column 2, p.1177 teaches testing IL-2, IL-4, IL-10 and IFNγ concentrations in sera from blood of MSC-treated and untreated immunized mice using Th1/Th2 ELISA Ready-Set-Go Kit. Augello does not teach the use of ELISA for the purpose of assessing interleukin 1-β).
Eastgate (paragraph 4, column 2, p. 706) teaches plasma samples…. The addition of 2 volumes of chloroform to 1 of plasma, mixing for 5 minutes, and then centrifugation at 10000g and removal of the aqueous phase for IL-1 beta testing in an enzyme-linked immunoabsorbent assay (IL-1 beta ELISA; Cistron Biotechnology/Laboratory Impex).
Therefore, it would be obvious before the effective filling date of the claim invention to be motivated to assess IL-1β by use of ELISA because (Eastgate paragraph 4 column 1, p.708) teaches the extraction procedure increased the detection of plasma IL-1 beta which (Eastgate, abstract) correlates with disease activity.
Claim(s) 6 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis”, Audrea Augello et. al., 2007, hereinafter Augello, in view of Correlation of Plasma Interleukin1 levels with Disease Activity in Rheumatoid Arthritis”, Julie A. Eastgate et. al., 1988 hereinafter Eastgate, in view of Cytokines as Biomarkers in Rheumatoid Arthritis”, Agata Burska et. al. 2014, hereinafter Burska
Regarding claim 6 Augello et. al (paragraph 6, column 2, p. 117 teaches testing IL-2, IL-4, IL-10 and INFγ concentration in sera from blood of MSC treated mice. Concentrations of IL-2, IL-4, IL-10, IFN, and TNF in supernatants…..were also assessed. Augello and Eastgate does not teach using a stabilizing agent of plasma levels of IL-1β).
Burska (paragraph 5, p.5) teaches cytokine measurements were shown to be affected by the anticoagulant used and cytokine stability also appears increased in EDTA plasma perhaps through EDTA’s role as a protease inhibitor.
Therefore, it would have been obvious before the effective filling date of the claimed invention for a person of ordinary skill in the art to use EDTA as a stabilizing agent after blood collection to enhance IL-18 plasma levels because (Burksa) teaches the adding a stabilizing agent increase cytokine stability.
Regarding claim 8, modified Augello teaches wherein said stabilizing agent is a protease inhibitor (the stabilizing agent of a protease inhibitor is added by Burska as described above).
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis’” Audrea Augello et. al., 2007, hereinafter Augello, in view of Correlation of Plasma Interleukin1 levels with Disease Activity in Rheumatoid Arthritis”, Julie A. Eastgate et. al., 1988 hereinafter Eastgate, in view of Herbert (US2020/0096512A1)
Regarding claim 9 Augello (paragraph 12, p. 117) teaches testing IL-2, IL-4, IL-10 and INF γ concentration in sera from blood of MSC treated mice.) Eastgate(abstract) teaches the mean plasma level of interleukin 1 beta (IL-1 beta), measured by immunoassay, was significantly higher in 51 patients with rheumatoid. Augello and Eastgate does not teach the used of matrix metalloproteinases as a stabilizing agent.
Herbert [0083] teaches red blood cell enriched sample may also comprise….plasma/
serum, supernatant, and/or cell wash. Further Herbert [0142] teaches RBCs may have a capacity to sequester and release different proteins (e.g., cytokines..) and he degree of protein release (or alternatively sequestration) by RBCs is thought to be influenced by various factors arising during blood collection and processing. Moreover, Herbert [0150] teaches A red blood cell-enriched sample, or a red blood cell component may be contacted with one or more protease inhibitors…[0151] protease inhibitors suitable for use in the methods…. metalloproteases inhibitors.
Therefore, it would be obvious before the effective filling date of the claimed invention to use a matrix metalloprotease inhibitor because Herbert [0044-0046] teaches effect of protease inhibitors on the concentration of proteins from red blood cells and [0046-0047] teaches calmative data of cytokines released and the difference in the cumulative data of cytokines released from health individuals, healthy pregnant women, pregnant women with preeclampsia and oncology patients. The results [0250] shows relationship between protease inhibitors and changes in cytokine concentrations were unlikely related to the inhibition of non-specific proteolysis of the cytokines
Claim(s) 10 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over
Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis,” Audrea Augello et. al. 2007, hereinafter Augello, In view of Pre-analytical and biological variability in circulating interleukin 6 in healthy subjects and patients with rheumatoid arthritis”, Lene S Knudsen et. al. 2008 hereinafter Knudson
Regarding claim 10 Augello (fig 3, p. 1180 teaches serum concentrations of various cytokines. Augello does not teach assess and quantifying proinflammatory and anti-inflammatory mediators of plasma levels of IL-6.)
Knudsen et. al., (paragraph 6, p.64) teaches in table 1 the IL-6 concentrations in serum and different types of plasma in healthy subjects and rheumatoid arthritis (RA) patients. Circulating levels of IL-6 were significantly elevated in RA patients compared with healthy patients(p=0.005).
Therefore, it would obvious before the effective filling date of an ordinary person skilled in the art to analyze IL-6 plasma levels in patients because Knudsen (paragraph 6, p. 64) teaches the IL-6 concentrations in serum and plasma were elevated in RA patients which (Knudson abstract) aim was to determine analytical variability, a reference interval, and long- and short-term variation in serum and plasma IL-6 in healthy subjects and RA patients.
Regarding claim 11 Augello (paragraph 13, pp.1177-1178 teaches the use of Concentrations of IL-2, IL-4, IL-10, IFN, and TNF in supernatants of CII-primed T lymphocytes in vitro rechallenged with CII were also assessed Th1/Th2 ELISA Ready SetGo.) Augello does not teach measuring IL-6 via ELISA.
Knudsen (paragraph 2, p.61,) teaches serum and plasma concentrations of IL-6 were determined by a commercially available human IL-6 high-sensitive enzyme-linked immunosorbent assay from R&D and a standard curve was created with linear function and reliable numerical values between 0.156pg/mL and 10pg/mL).
Therefore, it would be obvious before the effective filling date of the claim invention for an ordinary person skill in the art to assess and quantify pro-inflammatory and anti-inflammatory mediators of plasma levels of interleukin-6 by use of ELISA because Knudsen(paragraph 3, p.60) teaches retrospective clinical studies of RA patients indicate serum or plasma concentrations IL-6 may be useful as a “prognosticator”….during treatment…with disease modifying antirheumatic drugs and (paragraph 4, p.73) the normal range for IL-6 concentrations ELISA are in accordance with the normal range reported in others using the same ELISA.
Claim(s) 12 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis,” Audrea Augello et. al., 2007, hereinafter Augello, in view of Correlation between plasma, synovial fluid and articular cartilage Interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee,” Youhua Wang et. al. 2013, hereinafter Wang
Regarding claim 12, Augello (paragraph 1-2, p. 1181 teaches observing that serum concentrations of IL-2 were not modified by the effect of MSCs (Figure 3A), while MSCs tended to decrease serum concentrations of IFNγ, IL-4, and IL-10 (Figure 3A). These data paralleled the results obtained in an analysis of supernatants of lymphocyte cultures, in which the presence of MSCs did not affect IL-2 concentrations, tended to reduce IFNγ and IL-4 concentrations, and significantly lowered concentrations of IL-10 (P = 0.0084) Figure 3B). Augello does not teach assessing and quantifying plasma levels of IL-18.
Wang (abstract, p.297) teaches an investigation of IL-18 levels in plasma, synovial fluid, and articular cartilage of patients with primary knee osteoarthritis (OA) (n = 33) to analyze their relationship with radiographic severity. Compared to healthy controls osteoarthritis patients had higher plasma and synovial fluid IL-18 concentrations (45.8 ± 22.1 vs. 23.7 ± 13.6 pg/ml, (P < 0.001) and 75.2 ± 40.1 vs. 28.3 ± 11.6 pg/ml, (P < 0.001).
Therefore, it would be obvious for a person of ordinary skill in the art before the effective filling date of the claim invention to assess and quantify plasma IL-18 levels because Wang (column 1, paragraph 2, p.301) inflammatory pathways are known to play a key role in the development of OA and many inflammatory cytokines and mediators could serve as a biochemical marker of the disease. This is beneficial for having a (Wang, column 1, paragraph 1, p.302) blood testing that is simple and easy to perform, has a strong practical value, and IL-18 useful in assessing disease severity with OA of the knee.
Regarding claim 13 Augello (paragraph 12, p. 1177 teaches using ELISA to test Il-2, Il-4, Il-10 and IFNγ concentration in sera of MSC-treated mice and untreated immunized mice. Augello does not teach using ELISA for quantifying and assessing IL-18 in plasma levels).
Wang (abstract) teaches compared to healthy controls osteoarthritis patients had higher plasma and synovial fluid IL-18 concentrations…. as measured by enzyme-linked immunosorbent assay.
Therefore, it would be obvious before the effective filling date of the claim invention for a person of ordinary skill in the art to apply ELISA techniques to measure plasma levels of interleukin-18 because Wang et. al (column 2, paragraph 2, p.302) showed IL-18 significantly correlated with the magnitude of the radiographic progression of OA, and the individual sample IL-18 levels were positively cross-correlation.
Claim(s) 14 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis,” Audrea Augello et. al., 2007, hereinafter Augello, in view of Correlation between plasma, synovial fluid and articular cartilage Interleukin-18 with radiographic severity in 33 patients with osteoarthritis of the knee,” Youhua Wang et. al. 2013, hereinafter Wang, in view Cytokines as Biomarkers in Rheumatoid Arthritis”, Agata Burska et. al. 2014, hereinafter Burska
Regarding claim 14 Augello (paragraph 12, p. 117 teaches testing IL-2, IL-4, IL-10 and INF γ concentration in sera from blood of MSC treated mice). Wang (abstract) teaches compared to healthy controls osteoarthritis patients had higher plasma and synovial fluid IL-18 concentrations…. as measured by enzyme-linked immunosorbent assay. Augello and Wang do not teach using a stabilizing agent of plasma levels of any proinflammatory cytokine including IL-18.
Burksa (paragraph 6, p.3) teaches sample handling factors (collection methods, storage, and plasma versus serum) may influence the measurement of cytokines and are also likely to change with not only therapy but also stress and cachexia). Moreover, Burksa (paragraph 5, p.5) discloses cytokine measurements were shown to be affected by the anticoagulant used and cytokine stability also appears increased in EDTA plasma perhaps through EDTA’s role as a protease inhibitor.
Therefore, it would have been obvious before the effective filling date of the claimed invention for a person of ordinary skill in the art to use EDTA as a stabilizing agent after blood collection to enhance IL-18 plasma levels because (Burksa) teaches the adding a stabilizing agent increase cytokine stability.
Regarding claim 16, modified Augello teaches wherein said stabilizing agent is a protease inhibitor (the stabilizing agent of a protease inhibitor is added by Burska as described above).
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis,” Audrea Augello et. al., 2007, hereinafter Augello, in view Frank Augello et. al (US 2004/0048384A1)
Regarding claim 14 (A. Augello paragraph 12, p. 117 teaches testing IL-2, IL-4, IL-10 and INF γ concentration in sera from blood of MSC treated mice.) (A. Augello) does not teach using a stabilizing agent of plasma levels of any proinflammatory cytokine including IL-18.
(F. Augello paragraph [0017]) teaches a method for stabilizing a biological sample, and particularly whole blood, immediately upon collection from the patient to inhibitor prevent gene induction stored at room temperature, (paragraph [0039]) the biological sample is a body fluid, such as plasma, serum, urine, cerebral spinal fluid, and sputum. (F. Augello Example 6 in paragraph [0091]) teaches changes over time if certain interleukin mRNA species...and whole blood test sample stabilized with a composition of tetradecyltrimethylammonium oxalate and tartaric acid. Moreover, (F. Augello, paragraphs [0034-0035, see Figs 6-7]) teaches a comparison of interleukin 18 without stabilizing agent and (paragraph [0036 see Fig 8]) with stabilizing agent in.
Therefore, it would be obvious for an ordinary person skilled in the art before the effective filling date of the claimed invention to use a stabilizing agent, because (F. Augello) paragraph [0058] teaches it has been found that collecting the biological sample directly from the patient, such as when collecting a whole blood Sample, and introducing the sample directly into the container containing the stabilizing agents, substantially prevents or reduces the gene transcription and the decomposition of the nucleic acids that otherwise occur when the sample is stored before combining with the stabilizing agent.
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis,” Audrea Augello et. al., 2007, hereinafter A. Augello, in view Frank Augello et. al (US 2004/0048384A1), hereinafter F.Augello, in view of Herbert (US2020/0096512A1)
Regarding claim 17 (A. Augello paragraph 12, p. 117) teaches testing IL-2, IL-4, IL-10 and INF γ concentration in sera from blood of MSC treated mice.) (F. Augello) paragraph [0047-0050] teaches examples of suitable stabilizing agents include cationic compounds, detergents, chaotropic Salts, ribonuclease inhibitors, chelating agents, quaternary amines, and mixtures thereof. (A. Augello and F. Augello) do not teach using matrix metalloprotease inhibitor as a stabilizing agent of plasma levels of any proinflammatory cytokine including IL-18.
Herbert [0145] teaches non-limiting examples of suitable blood stabilizing agent includes protease inhibitor. Also, Herbert [0150] teaches contacting a whole blood sample with one or more protease inhibitor that modulate the level of one or more proteins in the sample component. Moreover, Herbert [0151] teaches to determine the effect of individual protease inhibitors on the level of proteins one may choose a particular protease inhibitor may include specific inhibitor. Protease inhibitors that are suitable are ….metalloprotease inhibitor.
Therefore, it would be obvious before the effective filling date of the claimed invention to use matrix metalloprotease inhibitor as a stabilizing agent because Herbert [0008] teaches finding that RBCs are a source of a number of different proteins (e.g., cytokines, chemokines, and/or growth factors) at substantial levels. This is beneficial because Herbert [0008] findings teach inventors have found that the addition of protease inhibitors…modulates the levels of various proteins in samples from those having a disease or disorder.
Claim (s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis,” Audrea Augello et. al., 2007, hereinafter Augello, in view of A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis”, Christopher J. Centeno et. al. 2015, hereinafter Centeno
Regarding claim 18, Augello (column 1, paragraph 3, p.1175 teaches a single injection of bone marrow derived mesenchymal stem cells) prevented the occurrence of severe, irreversible damage to bone and cartilage.) Augello does not teach using bone marrow concentrate as a treatment.
Centeno (abstract, p.1) discloses clinical outcomes for symptomatic knee osteoarthritis in relation to higher and lower cell concentrations contained within a bone marrow concentrate treatment protocol. In addition, Centeno (column 1, paragraph 2, p.3) teaches on the day of the procedure, approximately 10–15 cc of whole bone marrow aspirate was harvested from 6 to 8 bone sites… Posterior Superior Iliac Crest.
Therefore, it would be obvious to for one of ordinary skill in the art before the effective filling date of the claim invention because Centero (column 1, paragraph 3 p.7) states an improved and reduced pain was observed in patients treated with BMC injections regardless of cellular dosage, however patients receiving a higher concentration reported a better pain outcome in comparison to a lower dosage.
Claim 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cell Therapy Using Allogeneic Bone Marrow Mesenchymal Stem Cells Prevents Tissue Damage in Collagen Induced Arthritis,” Audrea Augello et. al., 2007, hereinafter Augello, in view of Treatment of Knee Osteoarthritis with Bone Marrow–Derived Mononuclear Cell Injection: 12-Month Follow-up”, Valdis Goncars et. al. 2019, hereinafter Goncars
Regarding claim 19 Augello (paragraph 2, p. 1184 discloses after determining whether immunosuppressive function of MSCs would be in effect when a disease is already established by injecting allogeneic MCSs on day 21, with immunization boost, when mice already showed signs of disease; the MSC were able to prevent the occurrence of severe lesions in the joints of immunized mice.) Augello does not teach administration of bone-marrow derived mononuclear cells.
Goncars (abstract) teaches to evaluate the main symptoms of knee osteoarthritis (OA) and tissue structure changes after a single dose bone marrow-derived mononuclear cell (BM MNC) intra articular injection. Moreover, Goncars (abstract) teaches the single dose BM MNC partially reduces clinical signs of the knee osteoarthritis stage II/III and in some cases, decreases degenerative changes in the joint building tissue over 12-month period.
Therefore, it would be obvious before the effective filling date of the claim invention to use the administration of bone marrow mononuclear cells because Goncars (column 1, paragraph 1, p. 33) the bone marrow aspirate was processed in order to isolate mononuclear cells and reduce contamination with red blood cells and erythrocyte lysate. Goncars (column 2, paragraph 4-5, p.33) teaches the intra-articular injection of the BM MNCs is a safe manipulation with no serious side effects over the 12-month period and the BM MNC injection in majority of cases provides a statistically and clinically significant improvement of knee osteoarthritis of stage II-III symptoms at the 12-month period.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REESHEDA T JONES whose telephone number is (571)272-4039. The examiner can normally be reached 8:00am-5:00pm.
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/R.T.J./Examiner, Art Unit 1796
/MATTHEW D KRCHA/Primary Examiner, Art Unit 1796